Protein capture by G-quadruplex DNA for breast cancer profiling
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Authors
Sweet, Taylor
Issue Date
2018-08
Type
Electronic thesis
Thesis
Thesis
Language
ENG
Keywords
Chemistry
Alternative Title
Abstract
G-quadruplexes (G4s) are guanine-rich DNA sequences that fold both intermolecularly and intramolecularly to form four-stranded DNA structures. These structures come from self-stacking of two or more guanine quartets formed through hydrogen bonding. G4s can be further classified by their orientation such as parallel and antiparallel. Guanine quadruplex (G-quadruplex) structures are amongst the various structures found in aptamers. Aptamers have become an important alternative to antibodies as protein affinity reagents due to their comparable and sometimes even higher specificities than antibodies, their low to no immunogenicity, and their unlimited shelf life. However, aptamer discovery has had only limited success despite intensive efforts since their discovery in 1990. Recently, the McGown group introduced a new, human genome inspired "reverse" selection process to overcome some of these obstacles involved in aptamer discovery and enable greater representation of G4 structures due to the diversity found in the human genome. Instead of choosing an aptamer from a combinatorial library of random oligonucleotides for high affinity to a target protein as seen in the process SELEX, this approach uses G4-forming DNA sequences from the human genome to fish out specific-binding proteins from natural protein pools. We are particularly interested in G4-forming sequences in human oncogene promoter regions, where there is a tendency for G4 sequences to occur. The work described in this thesis focuses on protein capture from ductal carcinoma (breast cancer) tissue lysates of different stages by G4 sequences from the Rb, VEGF, and c-myc promoter regions. With these studies, we hope to eventually be able to profile cancers based on their stage and type.
Description
August 2018
School of Science
School of Science
Full Citation
Publisher
Rensselaer Polytechnic Institute, Troy, NY